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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Enhanced wild-type p53 expression by small activating RNA dsP53-285 induces cell cycle arrest and apoptosis in
Dengqiang Lin1, Li Meng1, Feifei Xu1
1Department of Urology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200025, P.R. China.
Abstract:
Malignant pheochromocytoma (PHEO) is diagnosed only when metastasis has occurred, making it less likely for patients to obtain the benefits of traditional chemotherapy. Anti-oncogene TP53 mutation has been detected in PHEO and is possibly related to disease progression. However, whether the upregulation of wild-type TP53 has antitumoral effects on PHEO remains completely unknown. In the present study, we used RNA activation (RNAa) technique to upregulate the expression of wild-type TP53 by transfecting synthetic dsP53‑285 into PHEO cell line PC12. We found that the upregulation of wild-type p53 blocked the transition of PC12 cells from the G0/G1 to the S phase, with induction of apoptosis. Additionally, the above-mentioned findings were attested in vivo. Most importantly, dsP53-285-induced antitumoral effects were reversible following co-transfection with siRNA that targeted p53 mRNA. Collectively, our results revealed that the upregulation of p53 and possibly other anti-oncogenes may provide a potential effective therapeutic strategy for PHEO.
Insights
Upregulating wild-type TP53 shows anti-tumor effects in pheochromocytoma (PHEO) models. This approach, using RNA activation, successfully inhibited PHEO cell growth and induced apoptosis, offering a potential new therapy for this rare cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Malignant pheochromocytoma (PHEO) often presents with metastasis, limiting traditional chemotherapy efficacy.
- TP53 mutations are observed in PHEO, suggesting a role in disease progression.
- The therapeutic potential of wild-type TP53 upregulation in PHEO is unexplored.
Purpose of the Study:
- To investigate the antitumoral effects of wild-type TP53 upregulation in PHEO.
- To explore RNA activation as a method to increase wild-type TP53 expression in PHEO cells.
Main Methods:
- Utilized RNA activation (RNAa) by transfecting synthetic dsP53‑285 into the PC12 PHEO cell line.
- Assessed cell cycle progression (G0/G1 to S phase transition) and apoptosis induction.
- Validated findings in vivo and examined reversibility using siRNA targeting p53 mRNA.
Main Results:
- Upregulation of wild-type p53 via RNAa inhibited PC12 cell proliferation by blocking G0/G1 to S phase transition.
- Induced apoptosis in PHEO cells.
- Demonstrated that these antitumoral effects were reversible upon p53 knockdown.
Conclusions:
- Wild-type TP53 upregulation exhibits significant antitumoral effects in PHEO models.
- RNA activation of TP53 presents a potential therapeutic strategy for malignant pheochromocytoma.
- Further research into TP53 and other anti-oncogenes could yield novel treatments for PHEO.
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